Ubiquitin specific proteases responsible for mcl-1 stability and uses thereof

Abstract

Use of a polypeptide selected from the group consisting of USP13, USP26, USP38, USP42 or USP46 as a screening tool for an agent for treating cancer.

1 - 9 . (canceled) 
     
     
         10 . A screening tool to identify an agent for treating cancer, comprising a Ubiquitin Specific Protease (USP) polypeptide selected from a) USP13, USP26, USP38, USP42, USP46; b) a functional fragment of a polypeptide USP13, USP26, USP38, USP42 or USP46 and exhibiting an activity of deubiquitination; and c) a polypeptide comprising an amino acid sequence having a 84% or more homology with a polypeptide consisting of USP13, USP26, USP38, USP42 or USP46 and exhibiting an activity of deubiquitination. 
     
     
         11 . The screening tool of  claim 10 , wherein the USP polypeptide is USP46, a functional fragment thereof, or a substantially homologous sequence thereof. 
     
     
         12 . A cell transformed with an expression vector comprising a polynucleotide encoding a USP polypeptide of  claim 10 , or a functional fragment thereof, wherein the cell expresses the USP polypeptide, or a functional fragment thereof, and wherein the cell, or a cell membrane thereof, functions as a screening tool for an agent for treating cancer. 
     
     
         13 . A method for screening an agent for treating cancer comprising the steps of:
 bringing the cell of  claim 12 , or a cell membrane thereof, into contact with a compound to be tested; and   analyzing whether or not Myeloid cell leukemia-1 (Mcl-1) protein is stabilized.   
     
     
         14 . The method of  claim 13 , wherein the agent for treating cancer is an agent which destabilizes an Mcl-1 protein. 
     
     
         15 . A method for screening an agent for treating cancer comprising the steps of:
 bringing the cell of  claim 12 , or a cell membrane thereof, into contact with a compound to be tested; and   analyzing the rate of ubiquitination.   
     
     
         16 . A method for treating cancer comprising administering to a patient in need thereof an effective amount of an agent which decreases the activity of a USP polypeptide of  claim 10 , or a functional fragment thereof. 
     
     
         17 . The method of  claim 16 , further comprising administering an agent active against cancer. 
     
     
         18 . A method for delaying the progression of cancer comprising administering to a patient in need thereof an effective amount of an agent which decreases the activity of a USP polypeptide of  claim 10 , or a functional fragment thereof.